The mammalian middle ear is unique among tetrapods (mammals, amphibians, reptiles, and birds), in that it contains three distinct ossicles (the malleus, incus, and stapes) that form an indirect and usually flexible coupling path between the eardrum and cochlea, for which the majority of the ossicular mass is concentrated away from the cochlear entry axis. This differs markedly from the middle ears of non-mammalian tetrapods, in which eardrum motions are transmitted to the cochlea more or less in a straight line via a rod-like columella structure. Many theories have been presented as to the functional consequences and possible advantages of this peculiar middle-ear arrangement, especially considering that mammals are capable of hearing to much higher frequencies than non-mammals (>100 kHz vs. <12 kHz), and these theories range from allowing the ossicles to adopt lower-inertia vibrational modes at higher frequencies; to providing added flexibility to protect th cochlea against high static pressures in the ear canal or impulsive stimuli; to leveraging the off-axis mass distribution and joint flexibility to reduce the amount of ossicular inertia transmitted o the cochlea in response to skull vibrations from self-generated sounds due to vocalizations, breathing, pumping blood, etc., and thus allowing more attention to be focused on the external sounds critical for survival. In this proposal, the functioning of the mammalian ossicular chain will be tested, using measurements of 3D motion due to air and bone-conducted stimuli and 3D displacements due to positive and negative static pressure in the ear canal; and modeled, producing anatomically accurate ?CT-based 3D models of the full middle ear with accurate representations of ossicular-joint flexibility and the optional incorporation of a coiled cochlear model for testing bone-conduction responses. The measurements will be performed, and models based, on human, cat, and mouse temporal bones, with their: 1) natural ossicular chains, as well as with modified versions that 2) alter its natural freedom of motion by fusing one or both ossicular joints, and that 3) remove its indirect coupling path and off-axis mass distribution by replacing the incus with a columella-like prosthesis directly connecting the long process of the malleus to the footplate or head of the stapes. The measurements and resulting models will be used to comparatively examine the role of middle-ear structure on: 1) sound transmission from the ear canal to the cochlea, especially at higher frequencies; 2) protection of the cochlea; and 3) the transmission of sound to the cochlea via bone conduction. Comparisons across the three proposed scientifically and clinically important mammalian species will help to clarify any functional changes caused by differences in mammalian middle-ear anatomy, while comparisons across the proposed ossicular chain modifications will allow clarification of the functional implications of the structural features unique to mammalian middle ears. The measurements and models with a prosthesis replacing the incus may additionally lead to new ideas for improving the clinical outcomes of middle-ear reconstruction surgeries.

Public Health Relevance

The lack of knowledge about the relationships between middle-ear structures and sound transmission has resulted in unsatisfactory and variable outcomes of middle-ear repairs, particularly at high frequencies where sound localization cues may be important for hearing in noisy situations. The proposed research is significant for hearing health because it will provide a basis for understanding the role the flexible ossicular chain plays in the sensitivity of mammalian hearing through both the air- and bone- conduction pathways. The experiments and models will contribute to our understanding of the protective role of flexibility in the three-bone ossicular chain, the role of 3D ossicular modes in reducing inertia and improving high-frequency hearing in the normal ear, and the functioning of pathological (e.g., otosclerotic) and surgically repaired middle ears with a prosthesis. The proposed research is also significant because it will clarify the role of ossicular chain mass and flexibility on bone-conduction hearing, which could lead to improved bone conduction diagnostics and hearing devices.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC005960-12
Application #
9204819
Study Section
Special Emphasis Panel (ZRG1-IFCN-B (02)M)
Program Officer
Watson, Bracie
Project Start
2003-04-01
Project End
2019-01-31
Budget Start
2017-02-01
Budget End
2018-01-31
Support Year
12
Fiscal Year
2017
Total Cost
$441,223
Indirect Cost
$166,230
Name
Stanford University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94304
Gottlieb, Peter K; Vaisbuch, Yona; Puria, Sunil (2018) Human ossicular-joint flexibility transforms the peak amplitude and width of impulsive acoustic stimuli. J Acoust Soc Am 143:3418
Khaleghi, Morteza; Puria, Sunil (2017) Attenuating the ear canal feedback pressure of a laser-driven hearing aid. J Acoust Soc Am 141:1683
O'Connor, Kevin N; Cai, Hongxue; Puria, Sunil (2017) The effects of varying tympanic-membrane material properties on human middle-ear sound transmission in a three-dimensional finite-element model. J Acoust Soc Am 142:2836
Santa Maria, Peter Luke; Gottlieb, Peter; Santa Maria, Chloe et al. (2017) Functional Outcomes of Heparin-Binding Epidermal Growth Factor-Like Growth Factor for Regeneration of Chronic Tympanic Membrane Perforations in Mice. Tissue Eng Part A 23:436-444
Gottlieb, Peter K; Li, Xiping; Monfared, Ashkan et al. (2016) First results of a novel adjustable-length ossicular reconstruction prosthesis in temporal bones. Laryngoscope 126:2559-2564
Aldaz, Gabriel; Puria, Sunil; Leifer, Larry J (2016) Smartphone-Based System for Learning and Inferring Hearing Aid Settings. J Am Acad Audiol 27:732-749
Shin, Dong Ho; Seong, Ki Woong; Puria, Sunil et al. (2016) A tri-coil bellows-type round window transducer with improved frequency characteristics for middle-ear implants. Hear Res 341:144-154
Woo, Seong Tak; Shin, Dong Ho; Lim, Hyung-Gyu et al. (2015) A New Trans-Tympanic Microphone Approach for Fully Implantable Hearing Devices. Sensors (Basel) 15:22798-810
Kim, Namkeun; Steele, Charles R; Puria, Sunil (2014) The importance of the hook region of the cochlea for bone-conduction hearing. Biophys J 107:233-41
Cho, Jin-Ho; Puria, Sunil; Gummer, Anthony W (2013) MEMRO 2012 - Middle-ear bridge between science and otology. Hear Res 301:2-3

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